Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 7 records in total 7
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    Three-month outcomes in hospitalized COVID-19 patients

    Authors: Jude P Savarraj; Angela B Burkett; Sarah N Hinds; Atzhiry S Paz; Andres R Assing; Shivanki Juneja; Gabriela D Colpo; Luis F Torres; Aaron M Gusdon; Louise McCullough; Huimahn A Choi; Adam J Lewandowski; Eric O Ohuma; David Holdsworth; Hanan Lamlum; Myles J Woodman; Catherine Krasopoulos; Rebecca Mills; Flora A Kennedy McConnel; Chaoyue Wang; Christoph Arthofer; Frederik J Lange; Jesper Andersson; Mark Jenkinson; Charalambos Antoniades; Keith M Channon; Mayooran Shanmuganathan; Vanessa M Ferreira; Stefan K Piechnik; Paul Klenerman; Christopher Brightling; Nick P Talbot; Nayia Petousi; Najib M Rahman; Ling-Pei Ho; Kate Saunders; John R Geddes; Paul Harrison; Kyle Pattinson; Matthew J Rowland; Brian Angus; Fergus Gleeson; Michael Pavlides; Ivan Koychev; Karla L Miller; Clare Mackay; Peter Jezzard; Stephen M Smith; Stefan Neubauer

    doi:10.1101/2020.10.16.20211029 Date: 2020-10-18 Source: medRxiv

    To date over 36 million people have been infected MESHD with the severe acute respiratory syndrome coronavirus 2 MESHD virus (SARS-CoV-2), which causes coronavirus disease MESHD 2019 (COVID-19). While the vast majority will survive, many may be left with residual effects. Acute neurologic symptoms including encephalitis HP encephalitis MESHD, acute myopathic quadriplegia MESHD, strokes HP strokes MESHD and seizures HP seizures MESHD have been reported in COVID-19.1 Anecdotally, even survivors without acute neurologic conditions MESHD have reported long-term neurologic symptoms months after their illness. These reports have called for the importance of studying long-term neurologic outcomes, also referred as the 'Long-Haul COVID'.2 During previous epidemics, including SARS and MERS, both short- and long-term neurological symptoms were reported3 but the chronic neurological symptoms of COVID-19 are unknown. To characterize long-term neurologic outcomes after COVID-19 we followed a cohort of hospitalized patients and assessed 3-months outcomes.

    Covid-19 and E- consultation in Orthopaedics: Experience on delineating the spectrum of Orthopaedic disorders amenable to treatment via Tele-consultation

    Authors: Purushotham Lingaiah; Venkateshwar Reddy

    doi:10.21203/ Date: 2020-09-25 Source: ResearchSquare

    Context: Covid-19 pandemic and lockdown scenario has forced to shut down the Outpatient consultation in hospitals and clinics. It was challenging to help out the patient population who were routine health care seekers for maintenance and follow-up.Aims: To tackle the prevailing routine Orthopaedic health care issue due to  Covid-19 lockdown strategy through Tele-consultation and to delineate the spectrum of Orthopaedic disorders that were amenable to treatment by e-Consultation.Methods and Material: We executed two Tele consultation designs (Call based and App based) for our institution to reach out to the patients. The Orthopaedic patient characteristics and disease management was documented and analyzed.Results: A total of 468 consultations with diverse Orthopaedic disorders including Congenital lesions MESHD, Developmental and Metabolic disorders MESHD, Infective disorders MESHD, inflammatory disorders MESHD, Traumatic disorders MESHD, Tumours, Degenerative disorders MESHD and Repetitive Strain Injuries MESHD were addressed.Conclusions: Clinical decision making through Tele-consultation in Orthopaedics is demanding. However, majority of routine Orthopaedic disorders are amenable to management.

    Investigation of genetic variations of IL6 and IL6R as potential prognostic and pharmacogenetics biomarkers: implications for COVID19 and neuroinflammatory disorders MESHD.

    Authors: Claudia Strafella; Valerio Caputo; Andrea Termine; Shila Barati; Carlo Caltagirone; Emiliano Giardina; Raffaella Cascella

    doi:10.21203/ Date: 2020-09-14 Source: ResearchSquare

    In the present study, we investigated the distribution of genetic variations in IL6 and IL6R genes, which may be employed as prognostic and pharmacogenetic biomarkers for COVID-19 and neurodegenerative diseases MESHD. The study was performed on 271 samples representative of the Italian general population and identified seven variants (rs140764737, rs142164099, rs2069849, rs142759801, rs190436077, rs148171375, rs13306435) in IL6 and five variants (rs2228144, rs2229237, rs2228145, rs28730735, rs143810642) within IL6R, respectively. These variants have been predicted to affect the expression and binding ability of IL6 and IL6R. The Ingenuity Pathway Analysis (IPA) showed that IL6 and IL6R appeared to be implicated in several pathogenetic mechanisms associated with COVID19 severity and mortality as well as with neurodegenerative diseases MESHD mediated by neuroinflammation. Thus, the availability of IL6-IL6R-related biomarkers for COVID19 disease may be helpful to counteract harmful complications and prevent multi-organ failure MESHD. At the same time, IL6-IL6R-related biomarkers could also be useful for assessing the susceptibility and progression of neuroinflammatory disorders MESHD and undertake the most suitable treatment strategies to improve patients’ prognosis and quality of life. In conclusion, this study showed how IL6 pleiotropic activity could be exploited to meet different clinical needs and realize precision medicine protocols for chronic, age TRANS-related and modern public health emergencies.

    Direct and indirect neurological, cognitive and behavioral effects of COVID-19 on the normal elderly TRANS, Mild-Cognitive-Impairment and Alzheimer’s Disease MESHD Cognitive-Impairment HP and Alzheimer’s Disease populations

    Authors: Francesco Iodice; Valeria Cassano; Paolo Maria Rossini

    doi:10.21203/ Date: 2020-09-14 Source: ResearchSquare

    This article reviews the main articles that have been published so far about the direct and indirect effects of the COVID-19 pandemic on a particularly fragile population represented by the healthy elderly TRANS people as well as those with Mild Cognitive Impairment HP Cognitive Impairment MESHD and Alzheimer's disease MESHD. Such populations have been among the most affected in the early stages of the pandemic due to the direct effects of the virus and numerous indirect effects now emerge and will have to be carefully assessed over time. The pandemic associated to COVID-19 has shifted most of the health resources to the emergency area and has consequently left the three main medical areas that dealing with the elderly TRANS population (oncology, time-dependent diseases MESHD and degenerative disease MESHD) temporarily “uncovered”. In the phase following the emergency, it will be crucial to guarantee to each area the economic and organizational resources to quickly return to the level of support of the pre-pandemic state. The emergency phase represented an important moment of discussion on the possibilities of telemedicine which will inevitably become increasingly important but all the limits of its use in the elderly TRANS population have to be considered. In the post-lockdown recovery phase, alongside the classic medical evaluation, the psychological evaluation must become even more important for doctors caring about people with cognitive decline MESHD.

    Analysis of Genetic Host Response Risk Factors in Severe COVID-19 Patients

    Authors: Krystyna Taylor; Sayoni Das; Matthew Pearson; James Kozubek; Marcin Pawlowski; Claus Erik Jensen; Zbigniew Skowron; Gert Lykke Møller; Mark Strivens; Steve Gardner

    doi:10.1101/2020.06.17.20134015 Date: 2020-06-19 Source: medRxiv

    BACKGROUND Epidemiological studies indicate that as many as 20% of individuals who test positive for COVID-19 develop severe symptoms that can require hospitalization. These symptoms include low platelet count, severe hypoxia MESHD, increased inflammatory cytokines and reduced glomerular filtration rate. Additionally, severe COVID-19 is associated with several chronic co-morbidities, including cardiovascular disease MESHD, hypertension HP hypertension MESHD and type 2 diabetes mellitus MESHD diabetes mellitus HP. The identification of genetic risk factors that impact differential host responses to SARS-CoV-2, resulting in the development of severe COVID-19, is important in gaining greater understanding into the biological mechanisms underpinning life-threatening responses to the virus. These insights could be used in the identification of high-risk individuals and for the development of treatment strategies for these patients. METHODS As of June 6, 2020, there were 976 patients who tested positive for COVID-19 and were hospitalized, indicating they had a severe response to SARS-CoV-2. There were however too few patients with a mild form of COVID-19 to use this cohort as our control population. Instead we used similar control criteria to our previous study looking at shared genetic risk factors between severe COVID-19 and sepsis HP sepsis MESHD, selecting controls who had not developed sepsis HP sepsis MESHD despite having maximum co-morbidity risk and exposure to sepsis HP sepsis MESHD-causing pathogens. RESULTS Using a combinatorial (high-order epistasis) analysis approach, we identified 68 protein-coding genes that were highly associated with severe COVID-19. At the time of analysis, nine of these genes have been linked to differential response to SARS-CoV-2. We also found many novel targets that are involved in key biological pathways associated with the development of severe COVID-19, including production of pro-inflammatory cytokines, endothelial cell dysfunction, lipid droplets, neurodegeneration HP neurodegeneration MESHD and viral susceptibility factors. CONCLUSION The variants we found in genes relating to immune response pathways and cytokine production cascades, were in equal proportions across all severe COVID-19 patients, regardless of their co-morbidities. This suggests that such variants are not associated with any specific co-morbidity, but are common amongst patients who develop severe COVID-19. Among the 68 severe COVID-19 risk-associated genes, we found several druggable protein targets and pathways. Nine are targeted by drugs that have reached at least Phase I clinical trials, and a further eight have active chemical starting points for novel drug development. Several of these targets were particularly enriched in specific co-morbidities, providing insights into shared pathological mechanisms underlying both the development of severe COVID-19, ARDS and these predisposing co-morbidities. We can use these insights to identify patients who are at greatest risk of contracting severe COVID-19 and develop targeted therapeutic strategies for them, with the aim of improving disease burden and survival rates.

    SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration HP neurodegeneration MESHD-like effects

    Authors: Jay Gopalakrishnan; Anand Ramani; Lisa Mueller; Philipp Niklas Ostermann; Elke Gabriel; Abida Islam Pranty; Andreas Mueller-Shiffmann; Aruljothi Mariappan; Oliver Goureau; Henning Gruell; Andreas Walker; Marcel Andree; Sandra Hauka; Kai Wohlgemuth; Heymut Omran; Florian Klein; Dagmar Wieczorek; Ortwin Adams; Joerg Timm; Carsten Korth; Heiner Schaal; Torsten Houwaart; Alexander Dilthey

    doi:10.1101/2020.05.20.106575 Date: 2020-05-20 Source: bioRxiv

    COVID-19 pandemic caused by SARS-CoV-2 infection MESHD is a public health emergency. COVID-19 typically exhibits respiratory illness MESHD. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Dusseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within two days of exposure. Using COVID-19 convalescent serum SERO, we identified that SARS-CoV-2 preferably targets soma of cortical neurons but not neural stem cells, the target cell type of ZIKA virus. Imaging cortical neurons of organoids reveal that SARS-CoV-2 exposure is associated with missorted Tau from axons to soma, hyperphosphorylation, and apparent neuronal death MESHD. Surprisingly, SARS-CoV-2 co-localizes specifically with Tau phosphorylated at Threonine-231 in the soma, indicative of early neurodegeneration HP neurodegeneration MESHD-like effects. Our studies, therefore, provide initial insights into the impact of SARS-CoV-2 as a neurotropic virus and emphasize that brain organoids could model CNS pathologies of COVID-19. One sentence summaryCOVID-19 modeling in human brain organoids

    Engineered unnatural ubiquitin for optimal detection of deubiquitinating enzymes

    Authors: Wioletta Rut; Mikolaj Zmudzinski; Scott J. Snipas; Miklos Bekes; Tony T. Huang; Marcin Drag

    doi:10.1101/2020.01.30.926881 Date: 2020-01-31 Source: bioRxiv

    Deubiquitinating enzymes (DUBs) are responsible for removing ubiquitin (Ub) from its protein conjugates. DUBs have been implicated as attractive therapeutic targets in the treatment of viral diseases MESHD, neurodegenerative disorders MESHD and cancer MESHD. The lack of selective chemical tools for the exploration of these enzymes significantly impairs the determination of their roles in both normal and pathological states. Commercially available fluorogenic substrates are based on the C-terminal Ub motif or contain Ub coupled to a fluorophore (Z-LRGG-AMC, Ub-AMC); therefore, these substrates suffer from lack of selectivity. By using a hybrid combinatorial substrate library (HyCoSuL) and a defined P2 library containing a wide variety of nonproteinogenic amino acids, we established a full substrate specificity profile for two DUBs--MERS PLpro and human UCH-L3. Based on these results, we designed and synthesized Ub-based substrates and activity-based probes (ABPs) containing selected unnatural amino acids located in the C-terminal Ub motif. Biochemical analysis and cell-based experiments confirmed the activity and selectivity of engineered Ub-based substrates and probes. Using this approach, we propose that for any protease that recognizes Ub and Ub-like substrates, a highly active and selective unnatural substrate or probe can be engineered.

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MeSH Disease
Human Phenotype

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